Involvement of circRNA_0007059 in the regulation of postmenopausal osteoporosis by promoting the microRNA-378/BMP-2 axis |
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Authors: | Shu Liu Chao Wang Jinyi Bai Xiaoming Li Jiabin Yuan Zhicai Shi Ningfang Mao |
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Institution: | 1. Department of Spinal Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China
Shu Liu, Chao Wang, and Jinyi Bai contributed equally to this study as coauthors.;2. Department of Spinal Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China |
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Abstract: | Increasing evidence suggests that postmenopausal osteoporosis (PMO), a severe disturbance, imposes heavy physical, psychosocial, and financial burdens and dramatically influences the quality of life of postmenopausal women. Circular RNAs (circRNAs) and microRNAs (miRs) play important roles in the occurrence and development of PMO. However, the roles of circRNAs and miRs in osteoporosis regulation still need to be further investigated. circRNAs with different expression levels in patients with PMO were screened via RNA-seq and bioinformatics analysis. We found that circ_0007059 was upregulated in patients with PMO and during osteoclastogenesis of human bone marrow stromal cells (hBMSCs). Next, we investigated the effect of circ_0007059 overexpression during osteoclastogenesis of hBMSCs. circ_0007059 overexpression attenuated hBMSC differentiation into osteoclasts in vitro. This was demonstrated by downregulated bone morphogenetic protein 2 (BMP-2) expression, upregulated osteoclast-specific gene expression, and TRAP staining. circ_0007059 was demonstrated to directly target miR-378, which in turn targeted BMP-2 via bioinformatics analysis and the dual-luciferase reporter assay. Transfection of the miR-378 mimic reversed the effect of circ_0007059 on the osteoclastogenesis of hBMSCs. These results suggest that circ_0007059 plays an important role in osteoclastogenesis via the miR-378/BMP-2 signaling pathway. Targeting the circ_0007059/miR-378/BMP-2 axis is possibly a novel idea in osteoporosis treatment. |
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Keywords: | bone morphogenetic protein 2 circ_0007059 miR-378 osteoclastogenesis postmenopausal osteoporosis |
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